Blog Archive

Monday, 1 September 2008

Weekly BioNews 25 Aug - 1 Sep 2008

Researchers from Monash University have designed a nano-sized "trojan horse" particle to ensure healing antioxidants can be better absorbed by the human body.

Dr Ken Ng and Dr Ian Larson from the University's Faculty of Pharmacy and Pharmaceutical Sciences have designed a nanoparticle, one thousandth the thickness of a human hair, that protects antioxidants from being destroyed in the gut and ensures a better chance of them being absorbed in the digestive tract.

Antioxidants are known to neutralise the harmful effect of free radicals and other reactive chemical species that are constantly generated by our body and are thought to promote better health.

Normally our body's own antioxidant defence is sufficient, but in high-risk individuals, such as those with a poor diet or those at risk of developing atherosclerosis, diabetes or Alzheimer's disease, a nutritional source of antioxidants is required.

Dr Larson said orally delivered antioxidants were easily destroyed by acids and enzymes in the human body, with only a small percentage of what is consumed actually being absorbed.

The solution is to design a tiny sponge-like chitosan biopolymeric nanoparticle as a protective vehicle for antioxidants. Chitosan is a natural substance found in crab shells.

"Antioxidants sit within this tiny trojan horse, protecting it from attack from digestive juices in the stomach," Dr Larson said.

"Once in the small intestine the nanoparticle gets sticky and bonds to the intestinal wall. It then leaks its contents directly into the intestinal cells, which allows them to be absorbed directly into the blood stream... "

DNA barcoding is a movement to catalog all life on earth by a simple standardized genetic tag, similar to stores labeling products with unique barcodes. The effort promises foolproof food inspection, improved border security, and better defenses against disease-causing insects, among many other applications.

But the approach as currently practiced churns out some results as inaccurately as a supermarket checker scanning an apple and ringing it up as an orange, according to a new Brigham Young University study. It was funded by the National Science Foundation and published in the prestigious Proceedings of the National Academy of Sciences.

With the International Barcode of Life project seeking $150 million to build on the 400,000 species that have been "barcoded" to date, this worthy goal warrants more careful execution, the BYU team says.

"To have that kind of data is hugely valuable, and the list of applications is endless and spans all of biology," said study co-author Keith Crandall, professor and chair of the Department of Biology at BYU. "But it all hinges on building an accurate database. Our study is a cautionary tale – if we're going to do it, let's do it right."

Proponents of DNA barcoding seek to establish a short genetic sequence as a way of identifying species in addition to traditional approaches based on external physical features. Their aim is to create a giant library full of these sequences. Scientists foresee a future handheld device like a supermarket scanner – a machine that would sequence a DNA marker from an organism, then compare it with the known encyclopedia of life and spit out the species' name...

Scientists at the California Institute of Technology (Caltech) have developed a simple process for mass producing molecular tubes of identical--and precisely programmable--circumferences. The technological feat may allow the use of the molecular tubes in a number of nanotechnology applications.

The molecular tubes are composed of wound-up strands of DNA. DNA has been considered an ideal construction material for self-assembling molecular structures and devices because two complementary DNA strands can automatically recognize and bind with each other. DNA has been used to form rigid building blocks, known as tiles, and these tiles can further assemble into extended lattice structures, including tubes. However, it has been difficult to control the diameters of such tubes.

Peng Yin, a senior postdoctoral scholar in bioengineering and computer science at Caltech's Center for Biological Circuit Design, along with his colleagues has designed a series of flexible, single-stranded DNA molecules, called single-stranded DNA tiles. Each single-stranded tile is exactly 42 bases long and contains four modular binding sites. By pairing up the complementary binding sites, these single-stranded tiles bind with each other in a particular orientation like Lego pieces snapped together, forming a tube composed of parallel DNA helices.

The circumference of the resulting tube is determined by the number of different 42-base pieces used in its construction. For example, four pieces create a tube with a circumference of 12 billionths of a meter (or 12 nanometers); five pieces, a 15-nanometer-circumference tube; and six pieces, an 18-nanometer tube...

Engineers at Georgia Tech have used skin cells to create artificial bones that mimic the ability of natural bone to blend into other tissues such as tendons or ligaments. The artificial bones display a gradual change from bone to softer tissue rather than the sudden shift of previously developed artificial tissue, providing better integration with the body and allowing them to handle weight more successfully. The research appears in the August 26, 2008, edition of the Proceedings of the National Academy of Sciences.

"One of the biggest challenges in regenerative medicine is to have a graded continuous interface, because anatomically that's how the majority of tissues appear and there are studies that strongly suggest that the graded interface provides better integration and load transfer," said Andres Garcia, professor in the George W. Woodruff School of Mechanical Engineering at the Georgia Institute of Technology.

Garcia and former graduate student Jennifer Phillips, along with research technician Kellie Burns and their collaborators Joseph Le Doux and Robert Guldberg, were not only able to create artificial bone that melds into softer tissues, but were also able to implant the technology in vivo for several weeks.

They created the tissue by coating a three-dimensional polymer scaffold with a gene delivery vehicle that encodes a transcription factor known as Runx2. They generated a high concentration of Runx2 at one end of the scaffold and decreased that amount until they ended up with no transcription factor on the other end, resulting in a precisely controlled spatial gradient of Runx2. After that, they seeded skin fibroblasts uniformly onto the scaffold. The skin cells on the parts of the scaffold containing a high concentration of Runx2 turned into bone, while the skin cells on the scaffold end with no Runx2 turned into soft tissue. The result is an artificial bone that gradually turns into soft tissue, such as tendons or ligaments...

At about this time next year, nearly all of the 2,800 wild, rare and domesticated grapes in a unique northern California genebank will have had their "genetic profile" or “fingerprint” taken. These fingerprints may help grape breeders pinpoint plants in the collection that have unusual traits--ones that might appeal to shoppers in tomorrow's supermarkets.

Other grapes might be ideal for scientists who are doing basic research.

The grape collection that Aradhya is fingerprinting encompasses vineyards and screened enclosures, called “screenhouses." It is part of what’s officially known as the ARS National Clonal Germplasm Repository for Tree Fruit and Nut Crops and Grapes, in Davis, Calif.

To glean a distinctive genetic fingerprint of each member of the collection, Aradhya uses pieces of genetic material--or DNA--known as microsatellite markers. Eight markers are all that are needed for a genetic fingerprint of more familiar grapes, like close relatives of those already used for making wine or raisins or for eating out-of-hand...

Oregon Health & Science University scientists have successfully produced functional auditory hair cells in the cochlea of the mouse inner ear. The breakthrough suggests that a new therapy may be developed in the future to successfully treat hearing loss. The results of this research was recently published by the journal Nature.

“One approach to restore auditory function is to replace defective cells with healthy new cells,” said John Brigande, Ph.D., an assistant professor of otolaryngology at the Oregon Hearing Research Center in the OHSU School of Medicine. “Our work shows that it is possible to produce functional auditory hair cells in the mammalian cochlea.”

The researchers specifically focused on the tiny hair cells located in a portion of the ear’s cochlea called the organ of Corti. It has long been understood that as these hair cells die, hearing loss occurs. Throughout a person’s life, a certain number of these cells malfunction or die naturally leading to gradual hearing loss often witnessed in aging persons. Those who are exposed to loud noises for a prolonged period or suffer from certain diseases lose more sensory hair cells than average and therefore suffer from more pronounced hearing loss...

Life Under The Laser: Unique Technology Illuminates Microscopic Activity In Body's Chemical Messenger System

ScienceDaily (Aug. 31, 2008)

Researchers at The University of Nottingham have developed a unique technology that will allow scientists to look at microscopic activity within the body’s chemical messenger system for the very first time, live as it happens.

The cutting edge laser technology has helped to attract £1.3 million from the MRC (Medical Research Council) for a five-year project that will offer a new insight into the tiny world of activity taking place within single cells and could contribute to the design of new drugs to treat human diseases such as asthma and arthritis with fewer side effects.

The team, involving scientists from the University’s Schools of Biomedical Science (Professor Steve Hill and Dr Steve Briddon) and Pharmacy (Dr Barrie Kellam), is concentrating on a type of specialised docking site (receptor) on the surface of a cell that recognises and responds to a natural chemical within the body called adenosine.

These A3-adenosine receptors work within the body by binding with proteins to cause a response within cells and are found in very tiny and highly specialised area of a cell membrane called microdomains. Microdomains contain a collection of different molecules that are involved in telling the cell how to respond to drugs or hormones...

A tiny wasp that lays its eggs under the skin of unwitting caterpillars belongs to one of the most diverse groups of insects on Earth. Now researchers report that its diversity is even higher than previously thought.

By combining ecological and genetic data with the painstaking detective work of taxonomy, the researchers have dramatically increased – nearly doubling – the estimated number of species reported of six very species-rich genera of parasitoid wasps.

The subfamily to which these wasps belong, Microgastrinae, gets its name from its tiny abdomen. The wasp itself is quite small, about the size of the lead at the tip of a pencil.

By looking at the physical characteristics (morphology) of more than 2,500 wasps, the taxonomists identified 171 provisional species of microgastrine braconid wasps. But a comparative sequence analysis of a piece of a specific gene, a technique called DNA barcoding, found that there were actually 313 provisional species.

All of the wasps were reared from caterpillars collected in Area de Conservación Guanacaste (ACG), a biological reserve in northwestern Costa Rica. A decades-long ecological inventory of the area conducted by University of Pennsylvania ecologists Daniel Janzen and Winnie Hallwachs revealed that the wasps are extraordinarily specific to the caterpillar hosts they attack...

ABC-transporters expressed on endothelial cell membranes efflux anti-HIV drugs Researchers at Tulane University Medical Center in New Orleans (USA) have discovered that drug-efflux pumps, belonging to the ATP-binding cassette (ABC) transporter family, are constitutively expressed on vascular endothelial cells. Transcripts for several different ABC-transporters, e.g. MDR-1 (P-gp) and MRPs, were detected in endothelial cells, obtained from brain, aortic artery, pulmonary artery, dermal microvessels and umbilical veins. The ABC-transporter mediated efflux mechanisms decreased intracellular concentrations of the anti-HIV drugs, saquinavir, an HIV protease inhibitor (HPI) and zidovudine, a nucleoside reverse transcriptase inhibitor (NRTI), which are critical components of highly active antiretroviral therapy (HAART) against HIV. Inhibition of ABC-transporters, by using verapamil or MK-571, was shown to increase the intracellular retention of these anti-HIV agents. The MRP transporters were found to play a more dominant role in drug-efflux from endothelial cells. Pre-incubation of cells with the MRP-inhibitor, MK-571 significantly enhanced the intracellular levels of anti-HIV drugs. This study, entitled 'MRP (ABCC) transporters-mediated efflux of anti-HIV drugs, saquinavir and zidovudine, from human endothelial cells,' will be published in the September 2008 issue of Experimental Biology and Medicine.

These investigations led by Dr. Debasis Mondal, an assistant professor of Pharmacology, and co-authored by Mr. Mark Eilers and Dr. Upal Roy, demonstrated the significance of blocking MRP-transporters on endothelial barriers of blood vessels, in order to increase the pharmacokinetic efficacy of both HPIs and NRTIs. Drug-efflux pumps expressed on the blood-brain-barrier (BBB) were previously known to decrease drug entry into the central nervous system (CNS), however, this is the first evidence that endothelial cells from other organs express functional ABC-transporters, as well. The functional expression of MRPs on vascular endothelial barriers implicates their crucial role in facilitating the persistence of sub-endothelial HIV reservoirs....

Researchers at Rutgers University and The University of Texas at Austin have reported a discovery that could help scientists develop drugs to fight the much-feared bird flu and other virulent strains of influenza.The researchers have determined the three-dimensional structure of a site on an influenza A virus protein that binds to one of its human protein targets, thereby suppressing a person's natural defences to the infection and paving the way for the virus to replicate efficiently. This so-called NS1 virus protein is shared by all influenza A viruses isolated from humans - including avian influenza, or bird flu, and the 1918 pandemic influenza virus.

A paper detailing this breakthrough discovery appears in the PNAS (Proceedings of the National Academy of Sciences) Early Edition and will be published in an upcoming issue of the PNAS print edition.

About 10 years ago, Professor Robert M. Krug at The University of Texas at Austin discovered that the NS1 protein binds a human protein known as CPSF30, which is important for protecting human cells from flu infection. Once bound to NS1, the human protein can no longer generate molecules needed to suppress flu virus replication. Now, researchers led by Rutgers Professor Gaetano T. Montelione and Krug identified the novel NS1 binding pocket that grasps the human CPSF30 protein.

"Our work uncovers an Achilles heel of influenza A viruses that cause human epidemics and high mortality pandemics," said Montelione, professor of molecular biology and biochemistry. "We have identified the structure of a key target site for drugs that could be developed to effectively combat this disease."

X-ray crystallography, which was carried out by Kalyan Das, Eddy Arnold, LiChung Ma and Montelione, identified the three-dimensional structure of the NS1 binding pocket. "The X-ray crystal structure gives us unique insights into how the NS1 and human protein bind at the atomic level, and how that suppresses a crucial antiviral response," said Das, research professor at Rutgers.

Rei-Lin Kuo, Jesper Marklund, Karen Twu and Krug at The University of Texas at Austin verified the key role of this binding pocket in flu replication by genetically engineering a change to a single amino acid in the NS1 protein's binding pocket, which in turn eliminated the protein's ability to grasp the human protein that is needed to generate antiviral molecules. These investigators then produced a flu virus with an NS1 pocket mutation and showed that this mutated virus does not block host defences, and as a consequence has a greatly reduced ability to infect human cells...

Terminally ill rodents with type 1 diabetes have been restored to full health with a single injection of a substance other than insulin by scientists at UT Southwestern Medical Center.Since the discovery of insulin in 1922, type 1 diabetes (insulin-dependent diabetes) in humans has been treated by injecting insulin to lower high blood sugar levels and prevent diabetic coma. New findings by UT Southwestern researchers, which appear online and in a future issue of the Proceedings of the National Academy of Sciences, suggest that insulin isn't the only agent that is effective. Leptin, a hormone produced by the body's fat cells, also lowers blood glucose levels and maintains them in a normal range for extended periods, they found.

"The fact that these animals don't die and are restored to normal health despite a total lack of insulin is hard for many researchers and clinicians to believe," said Dr. Roger Unger, professor of internal medicine and senior author of the study. "Many scientists, including us, thought it would be a waste of time to give leptin in the absence of insulin. We've been brainwashed into thinking that insulin is the only substance that can correct the consequences of insulin deficiency."

The mechanism of leptin's glucose-lowering action appears to involve the suppression of glucagon, a hormone produced by the pancreas that raises glucose levels. Normally, glucagon is released when the glucose, or sugar, level in the blood is low. In insulin deficiency, however, glucagon levels are inappropriately high and cause the liver to release excessive amounts of glucose into the bloodstream. This action is opposed by insulin, which tells the body's cells to remove sugar from the bloodstream.

In type 1 diabetes, which affects about 1 million people in the U.S., the pancreatic islet cells that produce insulin are destroyed. Type 1 diabetics must take insulin multiple times a day to metabolise blood glucose and regiment their diets. In comparison, patients with non-insulin dependent, or type 2, diabetes make insulin, but their bodies don't respond well to it. Type 2 diabetes affects between 18 million and 20 million people in this country....